Dry eye disease is a complex and multifactorial pathology in which inflammation and changes
to the tear film (instability and hyperosmolarity) play important roles. Dry eye disease is
very common, with an estimated global prevalence of 11.59% although other analyses conclude
to 50% of some populations suffering from dry eye. The condition has been traditionally
classified in two subtypes: aqueous tear deficiency (secondary to a deficit of production by
the lacrimal gland) and evaporative disease (secondary to a deficit of the lipid layer of the
tear film), but when the condition progresses, almost all patients present characteristics of
both subtypes. Meibomian gland dysfunction (MGD) is one of the conditions that is most
frequently associated with dry eye disease and leads to evaporative dry eye and alterations
of the ocular surface. The prevalence of MGD has been recently established between 21.2% and
29.5% in subjects of African and Caucasian race and higher among Arabs, Hispanics, and
Asians. Many risk factors exist for dry eye disease and MGD, including age and usage of
contact lens. Soft contact lenses (SCL) are used by hundreds of millions for visual
correction. The wear of SCL, however, has the potential to create or worsen dry eye signs and
symptoms. A comparative study has found that 39% of North-American wearers can be categorized
as symptomatic of contact lens dry eye and the proportion of uncomfortable users increases
with age. SCL wear can increase evaporative dry eye by weakening the lipid layer, which leads
to decreased stability of the tear film and increased evaporation. It also contributes to
aqueous dry eye etiology by reducing the tear volume. The wear of SCL has also been shown to
have a damaging effect on meibomian glands and, in some cases, on the conjunctival goblet
cells .
Arguments also support the role of SCL in the inflammation of the ocular surface, even in
asymptomatic patients. Thus, dry eye disease associated with SCL wear is a complex condition
that implies different mechanisms.
Cyclosporine A is a peptide produced by a fungus that has been used systemically for decades
for its potent immunomodulatory effects. Usage for dry eye disease in a topical 0.05%
oil-based formulation has been common since the early 2000s. On the ocular surface,
cyclosporine acts by inhibiting calcineurin, which subsequently blocks the activation of T
cells and prevents the release of cytokines, therefore reducing inflammation. It has been
shown to increase tear volume, goblet cell density and to reduce surface staining as well as
symptoms in dry eye patients. Divergent results have been observed on contact lens wearers,
although one study has found an amplified effect on contact lens wearers symptomatic of dry
eye when combining essential fatty acid supplements with topical cyclosporine. Despite having
been shown useful in the management of dry eye disease, the oil-based formulation is
considered having a low bioavailability. A new cyclosporine eyedrop has been approved in
Canada and the USA in the recent past years and is based on nanomicelle technology with a
concentration of 0.09%. This nano-micellar formulation could be more effective in delivering
the cyclosporine to the tissues and have been shown to reduce ocular surface staining, to
increase tear volume, and to be safe. Adverse events that are known to this product are mild,
such as transient pain at instillation for about 23% of patients.
Intense pulsed light (IPL) is a therapeutic process that has been used for many years in
dermatology and esthetics. The noncoherent pulses of light produce photo-biochemical effects
and, in the treatment of dry eye disease, the application on the skin around the orbit to
produces these effects on the meibomian glands and their surrounding tissue. The mechanisms
by which IPL improves signs and symptoms of dry eye are not fully understood, but the melting
of the meibum, the clogging of telangiectatic inflammatory vessels, the reduction of
epithelial turnover, the improvement in the collagen synthesis, a mitochondrial activity
enhancement (photo modulation), and the destruction of parasitic and bacterial species are
the main theoretical explanations. IPL has been shown to be an effective therapeutic option
to manage MGD.
Dozens of studies have shown that IPL reduces dry eye symptoms, increases tear break-up time,
improves the secreting function of the glands as well as the quality of the meibum and
reduces corneal staining. IPL is often combined with meibomian gland expression to maximize
the therapeutic effects; however, controlled studies have shown that IPL is largely
responsible of these effects and that it is the core mechanism of this combination. Two
studies have observed the effect of IPL on SCL users, with the conclusion that it is an
effective treatment for this population. IPL is considered to be a safe treatment.
Since SCL have been linked to both aqueous and evaporative etiologies or dry eye, this
research project aims to study the effect of combining these two treatments to target the
entirety of the tear film, believed to be essential to comfortable SCL wear. This study will
be a randomized clinical trial that contains two interventions: the 0.09% cyclosporine
eyedrops (Cequa) and IPL treatment. The main objective of this study is to establish if the
treatment of contact lens related dry eyes by the combination of 0.09% cyclosporine for 16
weeks and a standard IPL treatment (3 sessions) is more effective in relieving dry eye
symptoms when compared to 0.09% cyclosporine for 16 weeks with a sham IPL treatment (3
sessions). The secondary objectives are to compare the effects of each treatment combination
(0.09% cyclosporine+IPL vs 0.09% cyclosporine+sham) on signs of dry eye, to explore the
effects of cyclosporine 0.09% drops alone on contact lens wearers and to assess the security
profile of these interventions on SCL wearers.
Based on prior data from the f-CLDEQ-8 validation study, a major study on the cyclosporine
nanomicelle formulation and the first clinical trial on IPL for contact lens wearers, a
sample size of 44 participants (22/group) was calculated to be necessary to detect a
significant difference between the groups. 44 participants will thus be recruited from a
primary care optometric clinic and nearby clinics. Participation to the study will require 5
visits from the participants. The first visit will be a collection of data and the dispensing
of the 0.09% cyclosporine drops. 8 weeks later, the participants will present for their 2nd
visit, during which data will be collected once again and participants will be randomized to
either the treatment or the sham group and will receive their first treatment (IPL or sham
accordingly to the assignation). The 2 following visits, 3 weeks apart, will be for the 2
last IPL/sham treatments. A final visit will be for data collection 2 weeks after the last
IPL/sham treatment. Participants will take 0.09% cyclosporine for the whole 16 weeks.
A bilateral t-test for independent samples will be used to compare the difference in change
on the f-CLDEQ-8 between groups on the 16 weeks interval. Concerning the dry eye signs,
statistical treatment will be made to account for inter-eye correlation. Continuous variables
will be analyzed using a multi-level model to assess the difference in change between groups
on the 16 weeks interval. Discrete variable will be analyzed using a general linear model
(GLM) for the same comparison. Data will be handled in an intent-to-treat way.